Skip to content

Researchers map Notch mutations in bladder cancer.

Notch genes are a double-edged sword, in some cancers they have a harmful effect because they promote tumour growth, whilst in others they act as tumour suppressors. The reason is still unclear, making it impossible to predict the behaviour of Notch within each tumour, and complicating its use as a drug target.

Now, CNIO researchers clear this dilemma up for bladder cancer, in which it exerts an anti-tumour effect. This result calls for caution when using therapeutic strategies based on the deactivation of Notch, because they could increase the risk of developing bladder cancer.  The opensource study is published in The Journal of Clinical Investigation.

The researchers sequenced the exome, the part of the genome that is translated into proteins, for 17 bladder cancers, and detected Notch mutations using mouse models for the genetic inactivation of Notch, specifically in the bladder.  In addition to clarifying the role that Notch plays in bladder cancer, the fifth most frequent cancer among men in developed countries, the authors offer clues to understand the dual function of this family of genes.

The team state that their analysis of Notch mutations in bladder cancer, mouse models, cell-based assays and human cancer samples offer solid evidence that the Notch pathway plays a relevant role as a tumour suppressor in bladder cancer. This result is not a surprise. Many of the tumours in which Notch acts as a suppressor are cancers that arise in squamous cells, which are found in different organs, such as the oesophagus or the skin. The urinary bladder can give rise to squamous cell cancer, so the researchers hypothesized that Notch could act as a suppressor in this tissue.

The confirmation of this hypothesis supports the idea that Notch intervenes in the architecture of the so-called stratified epithelia, in which cells grow in superimposed layers, a type of growth that also takes place in the bladder.

The group as well as other investigators had previously described the anti-tumour effects of pharmacologic inhibitors of Notch in pre-clinical models of lung adenocarcinoma, where Notch is oncogenic; the team state that the current data suggest that caution must be taken in the clinical application of non-specific Notch pathway inhibition, because it could increase the incidence of squamous-type tumours, like in the bladder.

Source:  Centro Nacional de Investigaciones Oncologicas (CNIO)

 

NOTCH inactivation induces the appearance of mesenchymal regions in SCCs.  Representative examples of IHC stainings against the indicated proteins on the indicated tumor subtypes and regions. Note the drastic decrease of HES1 and E-cadherin and the increase of vimentin in the mesenchymal region.  NOTCH pathway inactivation promotes bladder cancer progression.  Serrano et al 2015.
NOTCH inactivation induces the appearance of mesenchymal regions in SCCs. Representative examples of IHC stainings against the indicated proteins on the indicated tumor subtypes and regions. Note the drastic decrease of HES1 and E-cadherin and the increase of vimentin in the mesenchymal region. NOTCH pathway inactivation promotes bladder cancer progression. Serrano et al 2015.

 

 

Healthinnovations View All

Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.

Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.

Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.

Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.

An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

One thought on “Researchers map Notch mutations in bladder cancer. Leave a comment

  1. This double sward action of the notch gene (s) could it has alternative splicing that my lead to different gene expression product whereby it express promotion in an instance and inhibit in the other.

Leave a Reply

Translate »